Date of Award
Doctor of Philosophy (PhD)
Increasing number of genes encoding PLP-dependent transcription regulators, MocR/GabR type regulators, have been identified in various bacterial genomes. However, only a handful of them, including MocR, PdxR and GabR have been studied experimentally. They control different aspects of the bacterial metabolism. Only GabR has reported crystallographic structures. MocR/GabR regulators possess a chimeric structure consisted of a WHTH DNA binding domain and an Aminotransferase-like regulation domain, which can bind PLP as an effector in transcription regulation. Such a chimeric construct presents an interesting case in molecular evolution. The regulation domains of All MocR/GabR type regulators loss their catalytic capacity during evolution and function as means of effector recognition and transcription regulation. A MocR/GabR homolog in Klebsiella pneumoniae has recent been studied; this homolog is currently named Duf161R (YczR), since it putatively controls a gene encoding a membrane protein annotated as "domain of unknown function 161". We have determined the three-dimensional crystal structure of the regulatory domain of YczR to a resolution of 1.79 Å. Our crystallographic studies has revealed the structure of a truncated regulation domain with PLP bound, and our spectroscopic studies has gained evidence to support at least partial transaminase-like catalytic activity of the regulation domain. Together with DNA binding studies, we start to shed light on a new case of MocR regulation and its currently unconfirmed biological function, which is likely augmenting pathogenesis via facilitating taurine trafficking in K. pneumoniae. During my Ph.D. program, I also worked on several other protein projects. I add two chapters to demonstrate the PTP1B project. Protein tyrosine phosphatase 1B (PTP1B) is an enzyme shown to play an important role in insulin regulation. PTP1B is a critical negative regulator of insulin and leptin signaling pathways by removing phosphate groups (PO43-) from insulin receptor and other post-receptor substrates. Previous studies have identified transition metal compounds that exhibit insulin mimetic effects. A plausible explanation is that vanadium-containing compounds and zinc-containing compounds inhibit PTP1B activity, which allows required phosphorylation reaction to proceed normally. Five specifically modified vanadium containing and zinc containing compounds have been synthesized. This research has determined the three-dimensional crystal structure of PTP1B and VO(acac)2 complex to a resolution of 2.2 Å. Furthermore, the kinetic data suggests a mixed inhibition because of the aqueous study of the vanadium complex.
Zheng, Yuanzhang, "YCZR, a New Case of PLP-Dependent MOCR/GABR Type Transcription Regulator in Klebsiella Pneumonia" (2019). Dissertations. 3378.
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Copyright © 2019 Yuanzhang Zheng
Available for download on Tuesday, April 06, 2021